Autism and duplication of 17q12q21.2 by array-CGH: a case report.

This study reports on a boy with autism who has an extra piece of chromosome 17. The child had delayed development, walking at 25 months and talking at 4 years, plus some physical differences. Special genetic testing found he had duplicated genes that affect brain development. This genetic change has been seen before in children with autism and other developmental problems.

This case report describes a male child with autism spectrum disorder (ASD) and a 5.6-Mb duplication at chromosome region 17q12q21.2, identified through array-CGH testing. The child presented with multiple physical features including strabismus, cryptorchidism, hypertelorism, and frontal bossing, along with significant developmental delays (walking at 25 months, talking at 4 years). The duplication encompasses 190 genes, including HNF-1B and LHX1, which are associated with neurological development. The LHX1 gene plays a role in GABA neuron migration and differentiation, affecting cortical development.

This chromosomal duplication has been previously linked to kidney diseases and behavioral disorders, supporting its potential role in ASD pathophysiology.

Array-CGH may be valuable for identifying genetic variants in ASD cases with multiple anomalies and severe developmental delays. The 17q12q21.2 duplication should be considered in differential diagnosis of ASD with associated physical features and significant delays.

Single case report limits generalizability. No comparison with other ASD cases or controls. Causal relationship between duplication and ASD cannot be definitively established from one case.

Autism spectrum disorder (ASD) affects cognitive development and social interaction on different levels. Genetic and environmental factors are associated with secondary ASD. Genetic inheritance is mainly polygenic, and 10% are copy number variations (CNVs). Array comparative genomic hybridization (array-CGH) is used to identify CNVs.

This report aimed to discuss autism spectrum disorder and its diagnosis by array comparative genomic hybridization, highlighting the association with the pathogenic duplication of 17q12q21.2. A male baby was born at 37 weeks' gestation by cesarean section. The child showed strabismus, cryptorchidism, hypertelorism, frontal bossing, and developmental delay, walking at 25 months and talking at 4 years. At the age of 2 years, array-CGH of peripheral blood revealed a 5.6-Mb 17q12q21.2 duplication or arr 17q12q21.2 (34,815,527-40,213.109)x3 encompassing 190 genes, including HNF-1B and LHX1.

The child was clinically diagnosed with ASD. Changes in the 17q12 segment, such as the duplication found, have been associated with the development of several problems in previous studies, mainly kidney diseases and behavioral disorders. Located at this chromosome region, HNF1's homeobox B codes a member of the superfamily containing homeodomain of transcription factors. Another gene associated with abnormalities in neurological development regarding 17q12 deletions is LHX1, as shown in this case study.

LHX1 plays a role in the migration and differentiation of GABA neurons, modulating the survival of pre-optical interneurons, thus affecting cellular migration and distribution in the cortex. Changes in this control result in flaws in interneuron development, contributing to the pathophysiology of psychiatric diseases.